Plp1 in the enteric nervous system is preferentially expressed during early postnatal development in mouse as DM20, whose expression appears reliant on an intronic enhancer.
Plp1 in the enteric nervous system is preferentially expressed during early postnatal development in mouse as DM20, whose expression appears reliant on an intronic enhancer.
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DOI：
10.3389/fncel.2023.1175614
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发表时间：
2023
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
最近，髓磷脂蛋白脂质蛋白基因（Plp1）被证明在小鼠肠神经系统（ENS）的神经胶质细胞中表达。然而，除此之外，人们对它在肠道中的表达知之甚少。为了解决这个问题，我们研究了不同年龄（出生后第 2、9、21 和 88 天）小鼠肠道中 Plp1 mRNA 和蛋白质水平的表达。在这项研究中，我们发现 Plp1 表达优先发生在出生后早期发育期间，主要以 DM20 亚型形式表达。蛋白质印迹分析表明，当从肠道分离时，DM20 根据其配方重量进行迁移。然而，当从大脑获取时，PLP 和 DM20 的迁移率都比预期的要快。 6.2hPLP(+)Z/FL 转基因利用人类 PLP1 基因的前半部分驱动 lacZ 报告基因的表达，重现了在肠道中观察到的天然基因的发育模式，表明它可以用作 Plp1 基因表达的代理。因此，源自 6.2hPLP(+)Z/FL 转基因的 β-半乳糖苷酶 (β-gal) 活性的相对水平表明，Plp1 表达在十二指肠中最高，并沿各节段向结肠依次降低。此外，从转基因中去除 wmN1 增强子区域（位于 Plp1 内含子 1 内）会导致整个发育过程中转基因 mRNA 水平和肠道 β-gal 活性显着降低，表明该区域包含对 Plp1 表达至关重要的调节元件。这与中枢神经系统和周围神经系统的早期研究一致，表明它可能是控制 Plp1 基因表达的常见（如果不是普遍的）方式。
Recently, the myelin proteolipid protein gene (Plp1) was shown to be expressed in the glia of the enteric nervous system (ENS) in mouse. However, beyond this, not much is known about its expression in the intestine. To address this matter, we investigated Plp1 expression at the mRNA and protein levels in the intestine of mice at different ages (postnatal days 2, 9, 21, and 88). In this study, we show that Plp1 expression preferentially occurs during early postnatal development, primarily as the DM20 isoform. Western blot analysis indicated that DM20 migrated according to its formula weight when isolated from the intestine. However, mobilities of both PLP and DM20 were faster than expected when procured from the brain. The 6.2hPLP(+)Z/FL transgene, which uses the first half of the human PLP1 gene to drive expression of a lacZ reporter gene, recapitulated the developmental pattern observed with the native gene in the intestine, indicating that it can be used as a proxy for Plp1 gene expression. As such, the relative levels of β-galactosidase (β-gal) activity emanating from the 6.2hPLP(+)Z/FL transgene suggest that Plp1 expression is highest in the duodenum, and decreases successively along the segments, toward the colon. Moreover, removal of the wmN1 enhancer region from the transgene (located within Plp1 intron 1) resulted in a dramatic reduction in both transgene mRNA levels and β-gal activity in the intestine, throughout development, suggesting that this region contains a regulatory element crucial for Plp1 expression. This is consistent with earlier studies in both the central and peripheral nervous systems, indicating that it may be a common (if not universal) means by which Plp1 gene expression is governed.
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影响因子：
14.9
作者：
Baldarelli RM;Smith CM;Finger JH;Hayamizu TF;McCright IJ;Xu J;Shaw DR;Beal JS;Blodgett O;Campbell J;Corbani LE;Frost PJ;Giannatto SC;Miers DB;Kadin JA;Richardson JE;Ringwald M
通讯作者：
Ringwald M
影响因子：
5.5
作者：
Boesmans W;Nash A;Tasnády KR;Yang W;Stamp LA;Hao MM
通讯作者：
Hao MM
影响因子：
5.3
作者：
Patyal, Pankaj;Fil, Daniel;Hamdan, Hamdan;Wight, Patricia A.
通讯作者：
Wight, Patricia A.
DOI：
10.1073/pnas.84.16.5665
发表时间：
1987-08-01
影响因子：
11.1
作者：
NAVE, KA;LAI, C;MILNER, RJ
通讯作者：
MILNER, RJ
影响因子：
6.2
作者：
Boesmans, Werend;Lasrado, Reena;Pachnis, Vassilis
通讯作者：
Pachnis, Vassilis